Polymers have been used in pharmaceutical compositions for many years for a variety of different reasons, including controlling the release rate of drug from the dosage form. Conventionally drugs are formulated in admixture with one or more polymers and the drug/polymer mixture is formed into dosage forms, e.g. tablets are formed by compounding. The drug is only released from the dosage form when the polymer is dissolved or degraded and hence the rate of drug release can be controlled, and specifically decreased.
More recently polymers have been used in the preparation of drug-polymer conjugates wherein the drug is covalently bound to the polymer. Two types of drug-polymer conjugate have been prepared, one wherein the drug forms part of the polymer backbone and one wherein the drug is attached to a preformed polymer backbone. U.S. Pat. No. 6,613,807 discloses an example of the former wherein a drug-polymer conjugate comprising a polyanhydride backbone additionally comprises at least one group that will provide a therapeutically active compound upon hydrolysis of the polymer. US2014/0046018 discloses an example of the latter wherein a biodegradable polymer comprises a releasable bioactive moiety as a side group of its repeat unit.
The provision of drug-polymer conjugates is not, however, straightforward and a number of challenges need to be overcome. Covalently attaching biologically active molecules to preformed polymer backbones can be difficult to do because of steric and thermodynamic problems. This can impact on the distribution of biologically active molecule within the polymer and it can be difficult to achieve a high concentration of biologically active molecule in the polymer. As a result it can be impossible to provide compositions with adequately high biologically active molecule loading. It can also be difficult to control the release rate profile of biologically active molecule-polymer conjugates because the release rate depends on the degradation of bonds within the polymer. Assuming, as is typically the case, that all the biologically active molecule in the polymer is attached by the same type of bond, a burst of biologically active molecule release occurs when conditions that hydrolyse that type of bond are encountered and thereafter much lower amounts of biologically active molecule are released.
Another problem encountered in modern medicine is that an increasing number of diseases require combination therapy, i.e. treatment with more than one biologically active molecule within a treatment protocol. This is particularly the case in the treatment of infectious diseases and in cancer treatment. The drugs utilised in combination therapy often have complimentary modes of action and/or have additive or synergistic therapeutic effects. The treatment protocols employing multiple drugs are, however, invariably complicated and intensive. Frequent drug dosing and concomitant administration of several different drugs at a given point in time is commonplace. Such complicated protocols tend to have lower patient compliance and tolerance than more straightforward protocols.